scholarly journals Sulfur Administration in Fe–S Cluster Homeostasis

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1738
Author(s):  
Leszek Rydz ◽  
Maria Wróbel ◽  
Halina Jurkowska
Keyword(s):  
Oxidative Stress ◽  
Cluster Formation ◽  
Electron Donors ◽  
Cluster Assembly ◽  
Cysteine Desulfurase ◽  
Iron Sulfur Cluster ◽  
Sulfur Transfer ◽  
Iron Sulfur ◽  
Mercaptopyruvate Sulfurtransferase ◽  
Nuclear Cluster

Mitochondria are the key organelles of Fe–S cluster synthesis. They contain the enzyme cysteine desulfurase, a scaffold protein, iron and electron donors, and specific chaperons all required for the formation of Fe–S clusters. The newly formed cluster can be utilized by mitochondrial Fe–S protein synthesis or undergo further transformation. Mitochondrial Fe–S cluster biogenesis components are required in the cytosolic iron–sulfur cluster assembly machinery for cytosolic and nuclear cluster supplies. Clusters that are the key components of Fe–S proteins are vulnerable and prone to degradation whenever exposed to oxidative stress. However, once degraded, the Fe–S cluster can be resynthesized or repaired. It has been proposed that sulfurtransferases, rhodanese, and 3-mercaptopyruvate sulfurtransferase, responsible for sulfur transfer from donor to nucleophilic acceptor, are involved in the Fe–S cluster formation, maturation, or reconstitution. In the present paper, we attempt to sum up our knowledge on the involvement of sulfurtransferases not only in sulfur administration but also in the Fe–S cluster formation in mammals and yeasts, and on reconstitution-damaged cluster or restoration of enzyme’s attenuated activity.

The cysteine desulfurase IscS of Mycobacterium tuberculosis is involved in iron–sulfur cluster biogenesis and oxidative stress defence

2014 ◽  
Vol 459 (3) ◽  
pp. 467-478 ◽  
Author(s):  
Jan Rybniker ◽  
Florence Pojer ◽  
Jan Marienhagen ◽  
Gaëlle S. Kolly ◽  
Jeffrey M. Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mycobacterium Tuberculosis ◽  
Interaction Network ◽  
Cluster Assembly ◽  
Cysteine Desulfurase ◽  
Iron Sulfur Cluster ◽  
Sulfur Cluster ◽  
Iron Sulfur ◽  
Altered Surface ◽  
Made In

IscS of Mycobacterium tuberculosis is an essential component of iron–sulfur cluster assembly conferring resistance to oxidative stress. The strongly altered surface structure and the extensive protein-interaction network identified in the present study mirrors adaptations made in response to a heavily depleted mycobacterial ISC operon.

scholarly journals N-terminal tyrosine of ISCU2 triggers [2Fe-2S] cluster synthesis by ISCU2 dimerization

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sven-A. Freibert ◽  
Michal T. Boniecki ◽  
Claudia Stümpfig ◽  
Vinzent Schulz ◽  
Nils Krapoth ◽  
...  
Keyword(s):  
De Novo ◽  
Cluster Formation ◽  
Cluster Assembly ◽  
Cysteine Desulfurase ◽  
Iron Sulfur Cluster ◽  
Mutant Proteins ◽  
Iron Sulfur ◽  
Initial Iron ◽  
Oppositely Charged

AbstractSynthesis of iron-sulfur (Fe/S) clusters in living cells requires scaffold proteins for both facile synthesis and subsequent transfer of clusters to target apoproteins. The human mitochondrial ISCU2 scaffold protein is part of the core ISC (iron-sulfur cluster assembly) complex that synthesizes a bridging [2Fe-2S] cluster on dimeric ISCU2. Initial iron and sulfur loading onto monomeric ISCU2 have been elucidated biochemically, yet subsequent [2Fe-2S] cluster formation and dimerization of ISCU2 is mechanistically ill-defined. Our structural, biochemical and cell biological experiments now identify a crucial function of the universally conserved N-terminal Tyr35 of ISCU2 for these late reactions. Mixing two, per se non-functional ISCU2 mutant proteins with oppositely charged Asp35 and Lys35 residues, both bound to different cysteine desulfurase complexes NFS1-ISD11-ACP, restores wild-type ISCU2 maturation demonstrating that ionic forces can replace native Tyr-Tyr interactions during dimerization-induced [2Fe-2S] cluster formation. Our studies define the essential mechanistic role of Tyr35 in the reaction cycle of de novo mitochondrial [2Fe-2S] cluster synthesis.

scholarly journals Characterization and Reconstitution of Human Lipoyl Synthase (LIAS) Supports ISCA2 and ISCU as Primary Cluster Donors and an Ordered Mechanism of Cluster Assembly

2021 ◽  
Vol 22 (4) ◽  
pp. 1598
Author(s):  
Amber L. Hendricks ◽  
Christine Wachnowsky ◽  
Brian Fries ◽  
Insiya Fidai ◽  
James A. Cowan
Keyword(s):  
Cluster Assembly ◽  
Paramagnetic Resonance ◽  
Iron Sulfur Cluster ◽  
Sulfur Transfer ◽  
Disease States ◽  
Isolation And Characterization ◽  
Iron Sulfur ◽  
Natural Iron ◽  
Lipoyl Synthase

Lipoyl synthase (LIAS) is an iron–sulfur cluster protein and a member of the radical S-adenosylmethionine (SAM) superfamily that catalyzes the final step of lipoic acid biosynthesis. The enzyme contains two [4Fe–4S] centers (reducing and auxiliary clusters) that promote radical formation and sulfur transfer, respectively. Most information concerning LIAS and its mechanism has been determined from prokaryotic enzymes. Herein, we detail the expression, isolation, and characterization of human LIAS, its reactivity, and evaluation of natural iron–sulfur (Fe–S) cluster reconstitution mechanisms. Cluster donation by a number of possible cluster donor proteins and heterodimeric complexes has been evaluated. [2Fe–2S]-cluster-bound forms of human ISCU and ISCA2 were found capable of reconstituting human LIAS, such that complete product turnover was enabled for LIAS, as monitored via a liquid chromatography–mass spectrometry (LC–MS) assay. Electron paramagnetic resonance (EPR) studies of native LIAS and substituted derivatives that lacked the ability to bind one or the other of LIAS’s two [4Fe–4S] clusters revealed a likely order of cluster addition, with the auxiliary cluster preceding the reducing [4Fe–4S] center. These results detail the trafficking of Fe–S clusters in human cells and highlight differences with respect to bacterial LIAS analogs. Likely in vivo Fe–S cluster donors to LIAS are identified, with possible connections to human disease states, and a mechanistic ordering of [4Fe–4S] cluster reconstitution is evident.

scholarly journals Iron–sulfur cluster biosynthesis

2008 ◽  
Vol 36 (6) ◽  
pp. 1112-1119 ◽  
Author(s):  
Sibali Bandyopadhyay ◽  
Kala Chandramouli ◽  
Michael K. Johnson
Keyword(s):  
Scaffold Proteins ◽  
Cluster Assembly ◽  
Cysteine Desulfurase ◽  
Iron Sulfur Cluster ◽  
Iron Sulfur ◽  
Eukaryotic Organisms ◽  
Almost All ◽  
Cluster Biosynthesis

Iron–sulfur (Fe–S) clusters are present in more than 200 different types of enzymes or proteins and constitute one of the most ancient, ubiquitous and structurally diverse classes of biological prosthetic groups. Hence the process of Fe–S cluster biosynthesis is essential to almost all forms of life and is remarkably conserved in prokaryotic and eukaryotic organisms. Three distinct types of Fe–S cluster assembly machinery have been established in bacteria, termed the NIF, ISC and SUF systems, and, in each case, the overall mechanism involves cysteine desulfurase-mediated assembly of transient clusters on scaffold proteins and subsequent transfer of pre-formed clusters to apo proteins. A molecular level understanding of the complex processes of Fe–S cluster assembly and transfer is now beginning to emerge from the combination of in vivo and in vitro approaches. The present review highlights recent developments in understanding the mechanism of Fe–S cluster assembly and transfer involving the ubiquitous U-type scaffold proteins and the potential roles of accessory proteins such as Nfu proteins and monothiol glutaredoxins in the assembly, storage or transfer of Fe–S clusters.

scholarly journals The iron-sulfur cluster assembly network component NARFL is a key element in the cellular defense against oxidative stress

2015 ◽  
Vol 89 ◽  
pp. 863-872 ◽  
Author(s):  
Monique V. Corbin ◽  
Davy A.P. Rockx ◽  
Anneke B. Oostra ◽  
Hans Joenje ◽  
Josephine C. Dorsman
Keyword(s):  
Oxidative Stress ◽  
Cluster Assembly ◽  
Iron Sulfur Cluster ◽  
Sulfur Cluster ◽  
Cellular Defense ◽  
Iron Sulfur ◽  
Network Component

Biogenesis and Transfer of Iron-Sulfur Clusters from Acidithiobacillus ferrooxidans

2013 ◽  
Vol 825 ◽  
pp. 198-201 ◽  
Author(s):  
Jian She Liu ◽  
Lin Qian ◽  
Chun Li Zheng
Keyword(s):  
Acidithiobacillus Ferrooxidans ◽  
Binding Protein ◽  
Cluster Assembly ◽  
Cysteine Desulfurase ◽  
Iron Sulfur Cluster ◽  
Iron Sulfur Clusters ◽  
Sulfur Cluster ◽  
Iron Sulfur ◽  
Iron Sulfur Proteins

Iron-sulfur (Fe-S) proteins are ubiquitous and participate in multiple essential functions of life. However, little is currently known about the mechanisms of iron-sulfur biosynthesis and transfer in acidophilic microorganisms. In this study, the IscS, IscU and IscA proteins from Acidithiobacillus ferrooxidans were successfully expressed in Escherichia coli and purified by affinity chromatography. The IscS was a cysteine desulfurase which catalyzes desulfurization of L-cysteine and transfer sulfur for iron-sulfur cluster assembly. Purified IscU did not have an iron-sulfur cluster but could act as a scaffold protein to assemble the [2Fe-2S] cluster in vitro. The IscA was a [4Fe-4S] cluster binding protein, but it also acted as an iron binding protein. Further studies indicated that the iron sulfur clusters could be transferred from pre-assembled scaffold proteins to apo-form iron sulfur proteins, the reconstituted iron sulfur proteins could restore their physiological activities.

scholarly journals Molecular mechanism of the dual regulation of bacterial iron sulfur cluster biogenesis by CyaY and IscX

2017 ◽  
Author(s):  
Salvatore Adinolfi ◽  
Rita Puglisi ◽  
Jason C. Crack ◽  
Clara Iannuzzi ◽  
Fabrizio Dal Piaz ◽  
...  
Keyword(s):  
Metabolic Pathway ◽  
Cluster Formation ◽  
Hybrid Approach ◽  
Cluster Assembly ◽  
Enzymatic Process ◽  
Iron Sulfur Cluster ◽  
Sulfur Cluster ◽  
Iron Sulfur ◽  
Binding Surface ◽  
Iron Concentrations

AbstractIscX (or YfhJ) is a protein of unknown function which takes part in the iron-sulfur cluster assembly machinery, a highly specialised and essential metabolic pathway. IscX binds to iron with low affinity and interacts with IscS, the desulfurase central to cluster assembly. Previous studies have suggested a competition between IscX and CyaY, the bacterial ortholog of frataxin, for the same binding surface of IscS. This competition could suggest a link between the two proteins with a functional significance. Using a hybrid approach, we show here that IscX is a modulator of the inhibitory properties of CyaY: by competing for the same site on IscS, the presence of IscX rescues the rates of enzymatic cluster formation which are inhibited by CyaY. The effect is stronger at low iron concentrations, whereas it becomes negligible at high iron concentrations. These results strongly suggest that iron-sulfur cluster assembly is an exquisite example of an enzymatic process which requires a double regulation under the control of iron as the effector.

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